552 research outputs found

    HYPERSEQUENT CALCULI FOR INTERMEDIATE PREDICATE LOGICS (Logic, Language, Algebraic system and Related Areas in Computer Science)

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    We report on the current status of our on-going project to develop well-behaved hypersequent calculi for intermediate predicate logics, such as the linearity axiom LIN: (φ → ψ) ∨ (ψ → φ) and the constant domain axiom CD: ∀x(φ∨ψ(x)) → φ∨∀xψ(x)

    Antitumor Compounds from Marine Actinomycetes

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    Chemotherapy is one of the main treatments used to combat cancer. A great number of antitumor compounds are natural products or their derivatives, mainly produced by microorganisms. In particular, actinomycetes are the producers of a large number of natural products with different biological activities, including antitumor properties. These antitumor compounds belong to several structural classes such as anthracyclines, enediynes, indolocarbazoles, isoprenoides, macrolides, non-ribosomal peptides and others, and they exert antitumor activity by inducing apoptosis through DNA cleavage mediated by topoisomerase I or II inhibition, mitochondria permeabilization, inhibition of key enzymes involved in signal transduction like proteases, or cellular metabolism and in some cases by inhibiting tumor-induced angiogenesis. Marine organisms have attracted special attention in the last years for their ability to produce interesting pharmacological lead compounds

    Tissue Intrinsic Fluorescence Spectra-Based Digital Pathology of Liver Fibrosis by Marker-Controlled Segmentation

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    Tissue intrinsic emission fluorescence provides useful diagnostic information for various diseases. Because of its unique feature of spectral profiles depending on tissue types, spectroscopic imaging is a promising tool for accurate evaluation of endogenous fluorophores. However, due to difficulties in discriminating those sources, quantitative analysis remains challenging. In this study, we quantitatively investigated spectral-spatial features of multi-photon excitation fluorescence in normal and diseased livers. For morphometrics of multi-photon excitation spectra, we examined a marker-controlled segmentation approach and its application to liver fibrosis assessment by employing a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. We formulated a procedure of internal marker selection where markers were chosen to reflect typical biochemical species in the liver, followed by image segmentation and local morphological feature extraction. Image segmentation enabled us to apply mathematical morphology analysis, and the local feature was applied to the automated classification test based on a machine learning framework, both demonstrating highly accurate classifications. Through the analyses, we showed that spectral imaging of native fluorescence from liver tissues have the capability of differentiating not only between normal and diseased, but also between progressive disease states. The proposed approach provides the basics of spectroscopy-based digital histopathology of chronic liver diseases, and can be applied to a range of diseases associated with autofluorescence alterations

    Coenzyme Q10 suppresses apoptosis of mouse pancreatic beta-cell line MIN6

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    Background: In mitochondrial diabetes, apoptosis of β-cells caused by mitochondrial stress plays an important role in impaired insulin secretion. Several studies have reported that coenzyme Q10 (CoQ10) has therapeutic effects on mitochondrial diabetes, but no reports have examined the fundamental effectiveness or mechanism of CoQ10 in mitochondrial diabetes. We previously reported in a Japanese article that CoQ10 has protective effects on pancreatic β-cells against mitochondrial stress using mouse pancreatic β-cell line MIN6 and staurosporine (STS). Here, we report that CoQ10 protects MIN6 cells against apoptosis caused by STS and describe the more detailed apoptotic cascade. Methods: Apoptosis of MIN6 cells was induced by 0.5 μM STS treatment for specific periods with or without 30 μM CoQ10. The apoptosis cascade in MIN6 cells was then investigated using WST-8 assays, annexin-V staining, western blotting, and DNA degradation analysis. Results: Sixteen hours of 0.5 μM STS treatment led to 47% cell viability, but pretreatment with 30 μM CoQ10 resulted in significantly higher viability of 76% (P < 0.01). CoQ10 also prevented translocation of phosphatidylserine from the inner leaflet to the outer leaflet of the cell membrane. CoQ10 prevented cytochrome c release from mitochondria and activation of caspase-3. Conclusion: We concluded that CoQ10 protects pancreatic β-cells through anti-apoptotic effects against STS treatment

    Single-cell dynamics of pannexin-1-facilitated programmed ATP loss during apoptosis

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    死にゆく細胞のATP濃度変化を詳細に可視化することに成功 --積極的にATP濃度を下げる因子を明らかに--. 京都大学プレスリリース. 2020-10-22.ATP is essential for all living cells. However, how dead cells lose ATP has not been well investigated. In this study, we developed new FRET biosensors for dual imaging of intracellular ATP level and caspase-3 activity in single apoptotic cultured human cells. We show that the cytosolic ATP level starts to decrease immediately after the activation of caspase-3, and this process is completed typically within 2 hr. The ATP decrease was facilitated by caspase-dependent cleavage of the plasma membrane channel pannexin-1, indicating that the intracellular decrease of the apoptotic cell is a ‘programmed’ process. Apoptotic cells deficient of pannexin-1 sustained the ability to produce ATP through glycolysis and to consume ATP, and did not stop wasting glucose much longer period than normal apoptotic cells. Thus, the pannexin-1 plays a role in arresting the metabolic activity of dead apoptotic cells, most likely through facilitating the loss of intracellular ATP

    Isolation and characterization of a virus (CvV-BW1) that infects symbiotic algae of Paramecium bursaria in Lake Biwa, Japan

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    <p>Abstract</p> <p>Background</p> <p>We performed an environmental study of viruses infecting the symbiotic single-celled algae of <it>Paramecium bursaria </it>(<it>Paramecium bursaria Chlorella </it>virus, PBCV) in Lake Biwa, the largest lake in Japan. The viruses detected were all <it>Chlorella variabilis </it>virus (CvV = NC64A virus). One of them, designated CvV-BW1, was subjected to further characterization.</p> <p>Results</p> <p>CvV-BW1 formed small plaques and had a linear DNA genome of 370 kb, as judged by pulsed-field gel electrophoresis. Restriction analysis indicated that CvV-BW1 DNA belongs to group H, one of the most resistant groups among CvV DNAs. Based on a phylogenetic tree constructed using the <it>dnapol </it>gene, CvV was classified into two clades, A and B. CvV-BW1 belonged to clade B, in contrast to all previously identified virus strains of group H that belonged to clade A.</p> <p>Conclusions</p> <p>We conclude that CvV-BW1 composes a distinct species within <it>C. variabilis </it>virus.</p

    Spatial Evolution of Wave‐Particle Interaction Region Deduced From Flash‐Type Auroras and Chorus‐Ray Tracing

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    In-situ observations of spatial variations of the wave-particle interaction region require a large number of satellite probes. As an alternative, flash-type auroras, a kind of pulsating aurora, driven by discrete chorus elements, can be used to investigate the interaction region with a high spatial resolution. We estimated the spatial extent of wave-particle interaction region from ground-based observations of flash aurora at Gakona (62.39°N, 214.78°E), Alaska at subauroral latitudes, and found that the auroral expansion was predominantly to the low-latitude side. The spatial displacement is thought to be caused by the propagation effects of chorus waves in the magnetosphere. Using ray tracing analysis to take into account chorus wave propagation, we reconstructed the spatiotemporal evolution of the volume emission rate and confirmed that the predominant expansion is toward the lower-latitude side in the ionosphere. This study shows that chorus wave propagation in the magnetosphere gives new insight for characterizing the transverse size (across the geomagnetic field line) of wave-particle interaction regions. The calculated spatial scale of the column auroral emission shows a correlation with the magnetic latitude of the resonance region at magnetic latitudes within 10° of the equatorial plane of the magnetosphere. Our results suggest that the spatial scale of a flash aurora is indirectly related to the chorus amplitude because the latitudinal range of the wave-particle interaction is important for the growth of wave amplitude
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